Spinal cord injury can result from trauma, e g., in a car accident or fall from a horse, or from spinal cord ischemia which can occur during surgery that necessitates clamping the aorta, such as repair of vascular tears. Agonists of A2A adenosine receptors have been reported to reduce spinal cord inflammation and injury when administered immediately after spinal cord ischemia or trauma.
Adenosine signals through four G protein-coupled receptors: A1, A2A, A2B, and A3. Selective activation of A2ARs inhibits pro-inflammatory responses in bone marrow-derived cells including platelets, monocytes, some mast cells, neutrophils and T cells. A2A agonists have been found to protect many tissues, including heart, liver, kidney, and skin from ischemia-reperfusion injury when added during the reperfusion period. A2A agonists also have been found to reduce locomotor dysfunction following ischemia-reperfusion of traumatic injury to rabbit or pig spinal cord. This occurs at low doses that have no cardiovascular effects but that reduce spinal cord inflammation during reperfusion. Consistent with tissue protection mediated by endogenous adenosine acting on A2ARs, deletion of the A2AR gene has been shown to exacerbate liver and kidney reperfusion injury.
Currently, there is a need for methods and compounds for treatment or prevention of injuries to cells in the central nervous system (CNS).